Priming of the vascular endothelial growth factor signaling pathway by thrombospondin-1, CD36, and spleen tyrosine kinase

CD36 plays a critical role in the inhibition of angiogenesis through binding to the type 1 repeats of thrombospondin-1 (TSP-1) and activating Fyn tyrosine kinase and MAPK pathways. Here, we reveal a novel association of CD36 with VEGFR-2 and spleen tyrosine kinase (Syk). We also address the correlation between the expression of CD36 and Syk by demonstrating that overexpression of CD36 in HUVECs up-regulates endogenous Syk expression. We also define a new role for TSP-1 and CD36 in the activation of the VEGFR-2 signaling pathway that requires Syk. Our findings also identify a role for Syk as a stimulator of VEGF-A-induced angiogenesis by increasing phosphorylation of Y1175 in VEGFR-2, which is a major tyrosine for promoting VEGF-A-induced endothelial cell migration. Together, these studies introduce a new signaling pathway for TSP-1, CD36, and Syk, and address the role of these proteins in regulating the angiogenic switch.     

Angiosarcoma Presenting with Minor Erythema and Swelling

A 76-year-old man presented with slowly progressive swelling in his forehead and left upper eyelid over the course of three months. CT scanning showed non-specific enhancement of subcutaneous tissues, suggesting a low-grade cellulitis. Poor response to treatment prompted an MRI, which revealed the presence of a soft tissue lesion. Biopsy of this lesion was positive for angiosarcoma. The patient underwent chemotherapy and radiation, but unfortunately succumbed to his malignancy eight months later. This case illustrates a rare example of facial/periorbital angiosarcoma, a benign-appearing but aggressive tumor associated with a high incidence of mortality. A review of the literature and current treatment options are discussed.Key words: Tumor, Eyelid edema, Angiosarcoma, Eyelid cancer     

A National Experience on Physical Activity Initiatives for Adolescent Girls and their Mothers: CASPIAN Study

Objective

To provide a low-cost and simple model of culturally-appropriate and low cost facilities for improvement of physical activity for girls and their mothers through an after-school program and to determine the changes in anthropometric indexes after this trial.

Methods

This national study was conducted in 2006-2007 in 7 provinces with different socioeconomic situations in Iran. Female students who studied in the 7^th through 10^th grade and their mothers were selected by random cluster sampling. In each province, 24 sessions of after-school aerobic physical activity were held for 90 minutes, two days a week, and 3 months long at school sites in the afternoon.

Findings

The study comprised 410 participants (204 mothers and 206 daughters), with a mean age of 15.86±1.01 and 40.71±6.3 years in girls and their mothers, respectively. The results of the focus group discussions showed that in general, both mothers and daughters were satisfied from the program and found it feasible and successful. After the trial, the indexes of generalized and abdominal obesity improved significantly both in girls and in their mothers (P-value <0.0001 for weight, body mass index and waist circumference).

Conclusion

Our findings may provide a low-cost and simple effective model of motivation for physical activity with targeted interventions for girls and their mothers. We suggest that the success of this trial might be a result of bonding and accompaniment of mothers and daughters. Such model can be integrated in the existing health and education systems to increase the physical activity level.     

The prevalence of impaired fasting glucose and type 2 diabetes in a population‐based sample of overweight/obese children in the Middle East

Moadab MH, Kelishadi R, Hashemipour M, Amini M, Poursafa P. The prevalence of impaired fasting glucose and type 2 diabetes in a population‐based sample of overweight/obese children in the Middle East. Background: Type 2 diabetes mellitus (T2DM) and impaired fasting glucose (IFG) are increasing in young population who are facing an escalating trend of overweight. The aim of this study was to determine the prevalence of IFG and T2DM for the first time in a population‐based sample of Iranian obese children. Methods: This cross‐sectional, population‐based study was conducted in Isfahan, the second large city of Iran. Overall, 672 overweight and obese school students, selected from 7554 students, aged 6–19 yr, were screened for IFG and T2DM. Fasting plasma glucose (FPG) and lipid profile were measured in all participants. Oral glucose tolerance test and insulin level were measured in those children with IFG. Insulin resistance was defined as homeostasis model assessment for insulin resistance (HOMA‐IR) > 3.10. Results: Among the7554 students (48.7% boys and 51.3% girls) studied, 9.34% (n = 706) were overweight and 5.3% (n = 403) were obese. A number of 672 overweight and obese students including 302 (44.9%) boys and 370 (55.1%) girls, with a mean age of 12.8 ± 3.10 yr underwent biochemical work up. Overall, the prevalence of IFG was 4.61% (n = 31), the corresponding figure was 2% (n = 4) in the 6–10 yr age group, and 5% (n = 27) in those aged 10.1–19 yr. The prevalence of T2DM was 0.1% (n = 1; age, 18.00 yr). Impaired glucose tolerance and insulin resistance were detected in three and six participants with IFG, who consisted 0.4 and 0.8% of total obese and overweight students, respectively. Conclusions: Although the prevalence of T2DM is low in Iranian obese children, IFG is not uncommon. Preventive measures and screening of FPG should be considered for these children.     

Air pollution, platelet activation and atherosclerosis

Atherosclerosis begins in early life. The role of platelets is well-documented from its early stages. A wealth of evidence associates atherosclerotic cardiovascular disease with inflammatory diseases. The role of environmental factors, including air pollution, remains overlooked. Some studies have documented the effect of air pollution on inflammatory and pro-thrombotic factors implicated in the progression of cardiovascular diseases. In particular, the increase of platelet count and platelet hyper-reactivity towards agonists are emerging as markers of hematologic and hemostatic changes in response to the exposure to air pollutants. The systemic pro-inflammatory and pro-thrombotic response to the inhalation of fine and ultrafine particulate matters is seemingly associated with platelet activation. This association may have a clinical significance, particularly in the presence of cardiometabolic risk factors, and may indicate the need for anti-platelet treatment. It is of particular relevance to further study the significance of platelet activation and anti-platelet therapies in primordial/primary preventive measures in children and adolescents at risk of accelerated atherosclerosis.     

Consanguinity in primary immunodeficiency disorders; the report from Iranian Primary Immunodeficiency Registry

PROBLEM: Primary Immunodeficiency Disorders (PiD) are a heterogeneous group of genetic disorders, with different modes of inheritance. This study was accomplished in order to determine the frequency of consanguineous marriages in the families of patients with PiD. METHOD: In this study, the records 515 Iranian PiD patients were reviewed during a 25-year period. RESULTS: The mean proportion of consanguineous marriages was 65.6% among PiD patients, while the overall rate was 38.6% in the country. The rate of consanguinity was 77.8% in cellular immunodeficiencies, 75.8% in combined immunodeficiencies, 72.5% in defects of phagocytic function, 58.6% in other immunodefiiencies, 54.1% in predominantly antibody deficiencies, and 50% in complement deficiencies. Moreover all patients with immunodeficiency associated with other diseases had consanguineous parents. Such marriages were most common in the parents of patients with Chediak-Higashi syndrome, severe combined immunodeficiencies, primary CD4 deficiency, ataxia-telangiectasia, selective IgG class deficiencies, chronic granulomatous disease, and Schwachman syndrome. CONCLUSIONS: It is important to inform the general population about the dangers of consanguinity, which is very common in some areas such as Iran. Premarital examination to avoid genetic diseases could be suggested, especially in a community where the rate of consanguineous marriage is high.     

Topical morphine for the treatment of cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) is a potentially disfiguring parasitic disease which is endemic in many parts of the world. The evidence for optimal treatment of CL is uncongenial. The development of a compound used for the topical treatment of CL is an attractive option for overcoming the problems of toxic and expensive currently used anti-leishmanial drugs. Easy application is another attraction of topical treatment compared to systemic therapy. Evidence is certainly about a variety of immune responses in the healing process of CL. The immune modulatory effect of morphine also has been known in clinical medicine for decades. Protection against leishmaniasis is dependent upon generation of CD4(+) helper T-cells immune response. There are some evidences that opioids could be members of the cytokine family and the regulation of immune and inflammatory responses is dependent on the functions of cytokines; therefore much effort should be placed on understanding the effect of morphine on cytokine activity. Based on a previous mentioned evidence we suggest that morphine as an immunomodulator could induce the healing process of cutaneous leishmaniasis through inducing the release of a number of cytokines.